2023
Sex differences in the polygenic architecture of hearing problems in adults
De Angelis F, Zeleznik O, Wendt F, Pathak G, Tylee D, De Lillo A, Koller D, Cabrera-Mendoza B, Clifford R, Maihofer A, Nievergelt C, Curhan G, Curhan S, Polimanti R. Sex differences in the polygenic architecture of hearing problems in adults. Genome Medicine 2023, 15: 36. PMID: 37165447, PMCID: PMC10173489, DOI: 10.1186/s13073-023-01186-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultFemaleFollow-Up StudiesGenetic Predisposition to DiseaseGenome-Wide Association StudyHearingHumansMaleMultifactorial InheritanceSex CharacteristicsConceptsPolygenic architectureRisk lociGenome-wide investigationLarge-scale genetic studiesTranscriptomic regulationGWAS findingsTranscriptomic associationsGene interactionsPotential roleRegulation analysisGenetic studiesInference analysisMillion Veteran ProgramHealth Professionals FollowMolecular pathwaysPolygenic riskPreventive screening programsMultivariate interaction analysisNovel insightsCentral nervous systemEnvironmental risk factorsSex-stratified analysesSex-specific analysesSex differencesMental health outcomesEpidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders
Koller D, Pathak G, Wendt F, Tylee D, Levey D, Overstreet C, Gelernter J, Taylor H, Polimanti R. Epidemiologic and Genetic Associations of Endometriosis With Depression, Anxiety, and Eating Disorders. JAMA Network Open 2023, 6: e2251214. PMID: 36652249, PMCID: PMC9856929, DOI: 10.1001/jamanetworkopen.2022.51214.Peer-Reviewed Original ResearchMeSH KeywordsAnxietyDepressionEndometriosisFeeding and Eating DisordersFemaleGenome-Wide Association StudyHumansConceptsPsychiatric comorbidityMAIN OUTCOMEMental healthIrritable bowel syndromeBody mass indexAssociation of endometriosisOdds of depressionSevere physical symptomsPain-related phenotypesWomen's mental healthMultivariate regression analysisOdds of endometriosisBowel syndromeGenetic associationMass indexGynecologic pathologyMillion Veteran ProgramEndometriosisPsychiatric disordersWomen's healthFemale controlsPleiotropic mechanismsPhysical symptomsComorbiditiesFinnGen study
2022
Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records
Polimanti R, Wendt FR, Pathak GA, Tylee DS, Tcheandjieu C, Hilliard AT, Levey DF, Adhikari K, Gaziano JM, O’Donnell C, Assimes TL, Stein MB, Gelernter J. Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records. Molecular Psychiatry 2022, 27: 3961-3969. PMID: 35986173, PMCID: PMC10986859, DOI: 10.1038/s41380-022-01735-z.Peer-Reviewed Original ResearchConceptsCoronary artery diseasePosttraumatic stress disorderElectronic health recordsMillion Veteran ProgramArtery diseaseTotal scoreCAD diagnosisPlatelet amyloid precursor proteinHealth recordsPosttraumatic stress severityAmyloid precursor proteinEarly CAD diagnosisUK BiobankBidirectional relationshipTwo-sample Mendelian randomization (MR) analysisMendelian randomization analysisCAD riskHigh morbidityPTSD symptom severityCARDIoGRAMplusC4D consortiumPleiotropic mechanismsSymptom severityLongitudinal changesDiscordant effectsStress disorderAn Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes
Tylee DS, Lee YK, Wendt FR, Pathak GA, Levey DF, De Angelis F, Gelernter J, Polimanti R. An Atlas of Genetic Correlations and Genetically Informed Associations Linking Psychiatric and Immune-Related Phenotypes. JAMA Psychiatry 2022, 79: 667-676. PMID: 35507366, PMCID: PMC9069342, DOI: 10.1001/jamapsychiatry.2022.0914.Peer-Reviewed Original ResearchMeSH KeywordsAsthmaColitis, UlcerativeCrohn DiseaseGenome-Wide Association StudyHumansPhenotypePolymorphism, Single NucleotideRhinitis, AllergicConceptsRisk factorsImmune-related phenotypesMultivariable adjustmentUlcerative colitisCrohn's diseaseMendelian randomizationImmune-related disordersReciprocal risk factorsHealth-related behaviorsPsychiatric phenotypesFalse discovery rate correctionAllergic rhinitisGenetic association studiesGenetic associationInflammatory disordersClinical associationsMajor depressionImmune disordersMAIN OUTCOMEPsychiatric disordersSocial determinantsDisordersAssociation studiesColitisAsthmaUnderstanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways
Kasher M, Williams F, Freidin M, Malkin I, Cherny S, Benjamin E, Chasman D, Dehghan A, Ahluwalia T, Meigs J, Tracy R, Alizadeh B, Ligthart S, Bis J, Eiriksdottir G, Pankratz N, Gross M, Rainer A, Snieder H, Wilson J, Psaty B, Dupuis J, Prins B, Vaso U, Stathopoulou M, Franke L, Lehtimaki T, Koenig W, Jamshidi Y, Siest S, Abbasi A, Uitterlinden A, Abdollahi M, Schnabel R, Schick U, Nolte I, Kraja A, Hsu Y, Tylee D, Zwicker A, Uher R, Davey-Smith G, Morrison A, Hicks A, van Duijn C, Ward-Caviness C, Boerwinkle E, Rotter J, Rice K, Lange L, Perola M, de Geus E, Morris A, Makela K, Stacey D, Eriksson J, Frayling T, Slagboom E, Livshits G. Understanding the complex genetic architecture connecting rheumatoid arthritis, osteoporosis and inflammation: discovering causal pathways. Human Molecular Genetics 2022, 31: 2623-2632. PMID: 35349660, PMCID: PMC9402243, DOI: 10.1093/hmg/ddac061.Peer-Reviewed Original ResearchMeSH KeywordsArthritis, RheumatoidC-Reactive ProteinGenome-Wide Association StudyHumansInflammationMendelian Randomization AnalysisOsteoporosisPolymorphism, Single NucleotideConceptsCausal single nucleotide polymorphismsSingle nucleotide polymorphismsGenetic architectureColocalization analysisSame molecular functionAnalysis of pleiotropyComplex genetic architectureGenome-wide association study summary statisticsOp phenotypeMolecular functionsGenomic regionsPleiotropyOsteoporosis ConsortiumGenetic relationshipsGenetic backgroundGenetic variantsNucleotide polymorphismsMendelian randomizationGenesTraitsPhenotypeGenetic factorsProtein bindingUK BiobankHorizontal pleiotropy
2020
Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes
Georgakis M, Malik R, Gill D, Franceschini N, Sudlow C, Dichgans M, Lindstrom S, Wang L, Smith E, Gordon W, van Hylckama Vlieg A, de Andrade M, Brody J, Pattee J, Haessler J, Brumpton B, Chasman D, Suchon P, Chen M, Turman C, Germain M, Wiggins K, MacDonald J, Braekkan S, Armasu S, Pankratz N, Jackson R, Nielsen J, Giulianini F, Puurunen M, Ibrahim M, Heckbert S, Damrauer S, Natarajan P, Klarin D, de Vries P, SabaterLleal M, Huffman J, Bammler T, Frazer K, McCauley B, Taylor K, Pankow J, Reiner A, Gabrielsen M, Deleuze J, O’Donnell C, Kim J, McKnight B, Kraft P, Hansen J, Rosendaal F, Heit J, Psaty B, Tang W, Kooperberg C, Hveem K, Ridker P, Morange P, Johnson A, Kabrhel C, Trégouët D, Smith N, Benjamin E, Chasman D, Dehghan A, Ahluwalia T, Meigs J, Tracy R, Alizadeh B, Ligthart S, Bis J, Eiriksdottir G, Pankratz N, Gross M, Rainer A, Snieder H, Wilson J, Psaty B, Dupuis J, Prins B, Vaso U, Stathopoulou M, Franke L, Lehtimaki T, Koenig W, Jamshidi Y, Siest S, Abbasi A, Uitterlinden A, Abdollahi M, Schnabel R, Schick U, Nolte I, Kraja A, Hsu Y, Tylee D, Zwicker A, Uher R, Davey-Smith G, Morrison A, Hicks A, van Duijn C, Ward-Caviness C, Boerwinkle E, Rotter J, Rice K, Lange L, Perola M, de Geus E, Morris A, Makela K, Stacey D, Eriksson J, Frayling T, Slagboom E. Interleukin-6 Signaling Effects on Ischemic Stroke and Other Cardiovascular Outcomes. Circulation Genomic And Precision Medicine 2020, 13: e002872-e002872. PMID: 32397738, PMCID: PMC7299212, DOI: 10.1161/circgen.119.002872.Peer-Reviewed Original Research
2019
A polygenic resilience score moderates the genetic risk for schizophrenia
Hess JL, Tylee DS, Mattheisen M, Børglum A, Als T, Grove J, Werge T, Mortensen P, Mors O, Nordentoft M, Hougaard D, Byberg-Grauholm J, Bækvad-Hansen M, Greenwood T, Tsuang M, Curtis D, Steinberg S, Sigurdsson E, Stefánsson H, Stefánsson K, Edenberg H, Holmans P, Faraone S, Glatt S. A polygenic resilience score moderates the genetic risk for schizophrenia. Molecular Psychiatry 2019, 26: 800-815. PMID: 31492941, PMCID: PMC7058518, DOI: 10.1038/s41380-019-0463-8.Peer-Reviewed Original Research
2018
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
Ligthart S, Vaez A, Võsa U, Stathopoulou M, de Vries P, Prins B, Van der Most P, Tanaka T, Naderi E, Rose L, Wu Y, Karlsson R, Barbalic M, Lin H, Pool R, Zhu G, Macé A, Sidore C, Trompet S, Mangino M, Sabater-Lleal M, Kemp J, Abbasi A, Kacprowski T, Verweij N, Smith A, Huang T, Marzi C, Feitosa M, Lohman K, Kleber M, Milaneschi Y, Mueller C, Huq M, Vlachopoulou E, Lyytikäinen L, Oldmeadow C, Deelen J, Perola M, Zhao J, Feenstra B, Amini M, Lahti J, Schraut K, Fornage M, Suktitipat B, Chen W, Li X, Nutile T, Malerba G, Luan J, Bak T, Schork N, Del Greco M. F, Thiering E, Mahajan A, Marioni R, Mihailov E, Eriksson J, Ozel A, Zhang W, Nethander M, Cheng Y, Aslibekyan S, Ang W, Gandin I, Yengo L, Portas L, Kooperberg C, Hofer E, Rajan K, Schurmann C, Hollander W, Ahluwalia T, Zhao J, Draisma H, Ford I, Timpson N, Teumer A, Huang H, Wahl S, Liu Y, Huang J, Uh H, Geller F, Joshi P, Yanek L, Trabetti E, Lehne B, Vozzi D, Verbanck M, Biino G, Saba Y, Meulenbelt I, O’Connell J, Laakso M, Giulianini F, Magnusson P, Ballantyne C, Hottenga J, Montgomery G, Rivadineira F, Rueedi R, Steri M, Herzig K, Stott D, Menni C, Frånberg M, St. Pourcain B, Felix S, Pers T, Bakker S, Kraft P, Peters A, Vaidya D, Delgado G, Smit J, Großmann V, Sinisalo J, Seppälä I, Williams S, Holliday E, Moed M, Langenberg C, Räikkönen K, Ding J, Campbell H, Sale M, Chen Y, James A, Ruggiero D, Soranzo N, Hartman C, Smith E, Berenson G, Fuchsberger C, Hernandez D, Tiesler C, Giedraitis V, Liewald D, Fischer K, Mellström D, Larsson A, Wang Y, Scott W, Lorentzon M, Beilby J, Ryan K, Pennell C, Vuckovic D, Balkau B, Concas M, Schmidt R, de Leon C, Bottinger E, Kloppenburg M, Paternoster L, Boehnke M, Musk A, Willemsen G, Evans D, Madden P, Kähönen M, Kutalik Z, Zoledziewska M, Karhunen V, Kritchevsky S, Sattar N, Lachance G, Clarke R, Harris T, Raitakari O, Attia J, van Heemst D, Kajantie E, Sorice R, Gambaro G, Scott R, Hicks A, Ferrucci L, Standl M, Lindgren C, Starr J, Karlsson M, Lind L, Li J, Chambers J, Mori T, de Geus E, Heath A, Martin N, Auvinen J, Buckley B, de Craen A, Waldenberger M, Strauch K, Meitinger T, Scott R, McEvoy M, Beekman M, Bombieri C, Ridker P, Mohlke K, Pedersen N, Morrison A, Boomsma D, Whitfield J, Strachan D, Hofman A, Vollenweider P, Cucca F, Jarvelin M, Jukema J, Spector T, Hamsten A, Zeller T, Uitterlinden A, Nauck M, Gudnason V, Qi L, Grallert H, Borecki I, Rotter J, März W, Wild P, Lokki M, Boyle M, Salomaa V, Melbye M, Eriksson J, Wilson J, Penninx B, Becker D, Worrall B, Gibson G, Krauss R, Ciullo M, Zaza G, Wareham N, Oldehinkel A, Palmer L, Murray S, Pramstaller P, Bandinelli S, Heinrich J, Ingelsson E, Deary I, Mägi R, Vandenput L, van der Harst P, Desch K, Kooner J, Ohlsson C, Hayward C, Lehtimäki T, Shuldiner A, Arnett D, Beilin L, Robino A, Froguel P, Pirastu M, Jess T, Koenig W, Loos R, Evans D, Schmidt H, Smith G, Slagboom E, Eiriksdottir G, Morris A, Psaty B, Tracy R, Nolte I, Boerwinkle E, Visvikis-Siest S, Reiner A, Gross M, Bis J, Franke L, Franco O, Benjamin E, Chasman D, Dupuis J, Snieder H, Dehghan A, Alizadeh B, Alizadeh B, Boezen H, Franke L, van der Harst P, Navis G, Rots M, Snieder H, Swertz M, Wolffenbuttel B, Wijmenga C, Benjamin E, Chasman D, Dehghan A, Ahluwalia T, Meigs J, Tracy R, Alizadeh B, Ligthart S, Bis J, Eiriksdottir G, Pankratz N, Gross M, Rainer A, Snieder H, Wilson J, Psaty B, Dupuis J, Prins B, Vaso U, Stathopoulou M, Franke L, Lehtimaki T, Koenig W, Jamshidi Y, Siest S, Abbasi A, Uitterlinden A, Abdollahi M, Schnabel R, Schick U, Nolte I, Kraja A, Hsu Y, Tylee D, Zwicker A, Uher R, Davey-Smith G, Morrison A, Hicks A, van Duijn C, Ward-Caviness C, Boerwinkle E, Rotter J, Rice K, Lange L, Perola M, de Geus E, Morris A, Makela K, Stacey D, Eriksson J, Frayling T, Slagboom P. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders. American Journal Of Human Genetics 2018, 103: 691-706. PMID: 30388399, PMCID: PMC6218410, DOI: 10.1016/j.ajhg.2018.09.009.Peer-Reviewed Original ResearchConceptsC-reactive proteinAmount of CRPGenome-wide association studiesMendelian randomization analysisClinical outcomesChronic inflammationChronic low-grade inflammationLow-grade inflammationRandomization analysisBody mass indexBiology of inflammationCausal protective effectDistinct genetic lociRisk-increasing effectSilico functional analysisMass indexProtective effectClinical consequencesMultiple complex diseasesImmune pathwaysInflammationBipolar disorderSensitive biomarkerGenome analysisHighlight pathwaysGenetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data
Tylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R, Worrall BB, Levine AJ, Martinson JJ, Nejentsev S, Speed D, Fischer A, Mick E, Walker BR, Crawford A, Grant SFA, Polychronakos C, Bradfield JP, Sleiman PMA, Hakonarson H, Ellinghaus E, Elder JT, Tsoi LC, Trembath RC, Barker JN, Franke A, Dehghan A, Team T, Consortium T, Consortium T, Registry T, Group T, Consortium T, Faraone SV, Glatt SJ. Genetic correlations among psychiatric and immune‐related phenotypes based on genome‐wide association data. American Journal Of Medical Genetics Part B Neuropsychiatric Genetics 2018, 177: 641-657. PMID: 30325587, PMCID: PMC6230304, DOI: 10.1002/ajmg.b.32652.Peer-Reviewed Original ResearchConceptsImmune-related phenotypesPsychiatric disordersSystemic lupus erythematosusPrimary biliary cirrhosisLinkage disequilibrium score regressionImmune-related disordersAttention deficit hyperactivity disorderAutoimmune comorbiditiesDeficit hyperactivity disorderLupus erythematosusUlcerative colitisBiliary cirrhosisCrohn's diseaseObsessive-compulsive disorderMajor depressionImmunological stateSmoking behaviorTourette syndromeBipolar disorderAnorexia nervosaSummary-level dataEpidemiological literatureImmune signalingRespective disordersDisorders